Most children born small for gestational age (SGA) show catch-up growth dur- ing the first 2 years of life, but approximately 15% of them continue to be short throughout childhood, adolescence and in adulthood. The functional role of the polymorphisms in the genes involved in the pathway of insulin-like growth factors (IGFs) remains to be elucidated in determining SGA phenotype and SGA-related outcomes. In the IGFBP3 gene's promoter region we have identified 4 new polymor- phisms (-1112 G/A, -1239 G /A, -1510 C /T and -1556 G /A) in SGA children, three of which have turned out to be statistically significant when compared to controls. Moreover, a preliminary analysis of regulatory regions of the IGFBP3 gene has highlighted the presence of putative p53 binding consensus sequences. It has been already shown that p53 family members (p53, p63,p73) are involved in the IGFBP3 expression regulation. Indeed it has been reported that IGFBP3 is a p53 direct target. The aim of our study is to analyze in SGA children the functional significance of the polymorphisms we identified in the promoter region of IGFBP3 gene and to search whether the members of the p53 oncosuppressor gene family, in particular p63 and p73 proteins, are involved in the regulation of IGFBP3 gene expression.
Study of the regulation of the IGFBP3 gene expression in short children born small for gestational age
F Marzano;MF Caratozzolo;A Tullo
2009
Abstract
Most children born small for gestational age (SGA) show catch-up growth dur- ing the first 2 years of life, but approximately 15% of them continue to be short throughout childhood, adolescence and in adulthood. The functional role of the polymorphisms in the genes involved in the pathway of insulin-like growth factors (IGFs) remains to be elucidated in determining SGA phenotype and SGA-related outcomes. In the IGFBP3 gene's promoter region we have identified 4 new polymor- phisms (-1112 G/A, -1239 G /A, -1510 C /T and -1556 G /A) in SGA children, three of which have turned out to be statistically significant when compared to controls. Moreover, a preliminary analysis of regulatory regions of the IGFBP3 gene has highlighted the presence of putative p53 binding consensus sequences. It has been already shown that p53 family members (p53, p63,p73) are involved in the IGFBP3 expression regulation. Indeed it has been reported that IGFBP3 is a p53 direct target. The aim of our study is to analyze in SGA children the functional significance of the polymorphisms we identified in the promoter region of IGFBP3 gene and to search whether the members of the p53 oncosuppressor gene family, in particular p63 and p73 proteins, are involved in the regulation of IGFBP3 gene expression.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
